Field of the Invention
The present invention relates to an antimicrobial peptide and the manufacture thereof, and in particular relates to an antimicrobial peptide with high salt resistance, low hemolytic activity, and high protease resistance formed by linking a bulky amino acid and the N-terminal or C-terminal of the antimicrobial peptide.
Description of the Related Art
Various bioactive peptides have been reported in both the scientific literature and in issued patents. Peptides historically have been isolated from natural sources, and have recently been the subject of structure-function relationship studies. Additionally, natural peptides have served as starting points for the design of synthetic peptide analogs.
A review of peptide antibiotics was published by R. E. W. Hancock in 1997 (Lancet 349: 418-422). The structure, function, and clinical applications of various classes of peptides were discussed. An additional review of cationic peptide antibiotics was published in 1998 (Hancock, R. E. W. and Lehrer, R. Trends Biotechnol. 16: 82-88). The peptides are typically cationic amphipathic molecules of 12 to 45 amino acids in length. The peptides permeabilize cell membranes leading to the control of microbial agents. The clinical potential of host defense cationic peptides was discussed by R. E. W. Hancock in 1999 (Drugs 57(4): 469-473; Antimicrobial Agents and Chemotherapy 43(6): 1317-1323). The antibacterial, antifungal, antiviral, anticancer, and wound healing properties of the class of peptides are discussed.
The protective function of antimicrobial peptides in innate host defense mechanisms has been demonstrated in Drosophila, where reduced expression of such peptides dramatically decreases survival rates after microbial challenge. In mammals, a similar function is suggested by defective bacterial killing in the lungs of cystic fibrosis patients and in small mice.
The antimicrobial peptides found in mammals may be classified into the cysteine-rich defensins (α- and β-defensin) and various groups within the cathelicidin family. Based on the amino acid composition and structure, the cathelicidin family may be classified into three groups. The first group includes the amphipathic α-helical peptides such as LL-37, CRAMP, SMAP-29, PMAP-37, BMAP-27, and BMAP-28. The second group contains the Arg/Pro-rich or Trp-rich peptides including Bac5, Bac7, PR-39, and indolicidin. The third group includes Cys-containing peptides such as protegrins.
It is believed that non-antibiotic antimicrobial drugs, such as antimicrobial peptide, may be a main scheme of development for anti-microorganism agents in the future. Since antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today, the non-antibiotic antimicrobial drugs will be have a wide of industrial application in the field of aquaculture and livestock. Therefore, non-antibiotic antimicrobial drugs may solve the problems raised by abuse of antibiotics.
Although salt-resistance antibacterial peptides were published, it has a high hemolysis when its salt-resistance is increased. Thus, an antimicrobial peptide with high salt resistance, low hemolytic activity, and high protease resistance is required.